Klinik für Anästhesiologie und Intensivmedizin. Physiologie des Volumenersatzes - Rolle von balanzierten Lösungen. Matthias Heringlake

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1 Physiologie des Volumenersatzes - Rolle von balanzierten Lösungen Matthias Heringlake

2 Agenda Hintergrund Wieso balanziert? Aktuelle Datenlage Ist jetzt eigentlich alles geklärt? Schlussfolgerungen Potentielle Interessenskonflikte: Honorare und Forschungsunterstützung durch: Covidien-Medtronic, CAS Medical Systems, Orion Pharma, Tenax Pharma, Amomed Pharma

3 Agenda Hintergrund Wieso balanziert? Aktuelle Datenlage Ist jetzt eigentlich alles geklärt? Schlussfolgerungen

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5 Klinik für Anästhesiologie und Intensivmedizin Kapitel 4a: Unterschiede zwischen Kolloiden und Kristalloiden bei peri-interventionellen Patienten

6 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients

8 Klinik für Anästhesiologie Prinzip balancierter Lösungen: Ersatz von Chlorid durch metabolisierbare Anionen Beispiel: 1 mol Acetat > 1 mol HCO3- Zander - Flüssigkeitstherapie

9 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin A Randomized, Controlled, Double-Blind Crossover Study on the effects of 2-L Infusions of 0.9% Saline and Plasma-Lyte on Renal Blood Flow Velocity and Renal Cortical Tissue Perfusion in Healthy Volunteers. Initial plasma expansions of 29% and 26% of the infused volume were observed for Plasma-Lyte 148 and 0.9% saline, respectively. At the end of 4 hours, 14% of Plasma-Lyte 148 and 12% of 0.9% saline remained in the intravascular compartment. n = 12 Chowdhury et al. Ann Surg 2012;256:18 24)

10 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin A Randomized, Controlled, Double-Blind Crossover Study on the effects of 2-L Infusions of 0.9% Saline and Plasma-Lyte on Renal Blood Flow Velocity and Renal Cortical Tissue Perfusion in Healthy Volunteers. Wesentlicher Unterschied 0,9% Saline vs. Plasma Lyte: Chlorid: 156 vs. 98 mmol! n = 12 Chowdhury et al. Ann Surg 2012;256:18 24

11 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin Zusammensetzung häufig eingesetzter Kristalloide Sterofundin ISO- Osmolalität 309 mosmol/kg: Natrium 145; Kalium 4, Calcium 2,5 Chlorid 127 mmol/l, Acetat 24 mmol/l, Malat 5 mmol/l Plasma-Lyte A - Osmolarität 294 mosmol/kg - Natrium 140; Kalium 5, Magnesium 3; Chlorid 98 mmol/l, Acetat 27 mmol/l, Gluconat 5 mmol/l

13 Retrospektive sowie Meta-Analysen und Kohortenstudien Yunos NM et al. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA 2012;308: Krajewski ML et al. Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation. Br J Surg 2015;102: Shaw AD et al. Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte. Ann Surg 2012;255: Raghunathan K et al. Association Between the Choice of IV Crystalloid and In- Hospital Mortality Among Critically Ill Adults With Sepsis. Crit Care Med 2014; 42: Shaw AD et al. Association between intravenous chloride load during resuscitation and in-hospital mortality among patients with SIRS. Intensive Care Med 2014;40:

14 Association between Initial Fluid Choice and Subsequent In-hospital Mortality during the Resuscitation of Adults with Septic Shock Retrospective cohort study includes patients with severe sepsis who were resuscitated with at least 2 l of crystalloids and vasopressors by hospital day 2, patients who had not undergone any major surgical procedures, and patients who had a hospital length of stay (LOS) of at least 2 days. Raghunathan et al Anesthesiology 2015; 123: )

15 Association between Initial Fluid Choice and Subsequent In-hospital Mortality during the Resuscitation of Adults with Septic Shock Raghunathan et al Anesthesiology 2015; 123: )

16 Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit The SPLIT Randomized Clinical Trial The primary outcome was the proportion of patients with AKI, defined as a degree of renal dysfunction of injury or greater (based on the use of a 5-category scoring system to evaluate risk, injury, failure, loss, and end-stage renal failure [RIFLE]) based solely on defined thresholds of serum creatinine. Young P et al. JAMA. 2015;314(16):

17 Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit The SPLIT Randomized Clinical Trial Young P et al. JAMA. 2015;314(16):

18 Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit The SPLIT Randomized Clinical Trial Conclusions Among patients receiving crystalloid fluid therapy in the ICU, use of a buffered crystalloid compared with saline did not reduce the risk of AKI. Further large randomized clinical trials are needed to assess efficacy in higher-risk populations and to measure clinical outcomes such as mortality. Young P et al. JAMA. 2015;314(16):

19 Balanced Crystalloids versus Saline in the Intensive Care Unit: The SALT Randomized Trial Semler MW et al. AJRCCM Articles in Press.

20 Balanced Crystalloids versus Saline in the Intensive Care Unit: The SALT Randomized Trial Semler MW et al. AJRCCM Articles in Press.

21 Saline versus balanced solutions: are clinical trials comparing two crystalloid solutions really needed? Vincent and De Backer Critical Care (2016) 20:250

22 Saline versus balanced solutions: are clinical trials comparing two crystalloid solutions really needed? Undoubtedly, the safest intravenous solution in a patient without major metabolic abnormalities would have a composition close to that of human plasma. It has been said that bicarbonate is unstable when in solution, but this is not true as bicarbonate solutions are readily available from the shelf; actually, renal substitution fluids for continuous hemofiltration contain a mixture of electrolytes, including bicarbonate. Some people already administer these solutions as regular intravenous solutions but the 5-liter bag size complicates this practice. There are only a few indications for repeated saline administration: metabolic alkalosis (for the high chloride input) and hyponatremia (for the high sodium input), as well as severe brain injury for its normotonic composition. When such conditions are not present, administration of saline solutions should usually be restricted to not more than 1 liter per 24-h period. Vincent and De Backer Critical Care (2016) 20:250

24 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin Metabolisierbare Anionen Azetat und Laktat im Vergleich - Vorteile aufgrund von Grundlagendaten Zander - Flüssigkeitstherapie

25 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin Hepatic lactate uptake versus leg lactate output during exercise in humans Nielsen et al. J Appl Physiol 103: , 2007.

26 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin

27 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin Effects of acetate and bicarbonate dialysate in stable chronic dialysis patients. Hakim RM et al. Kidney Int 1985

28 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin Effects of acetate on energy metabolism and function in the isolated perfused rat heart. [%] dp/dt ATP Control Acetate 10 mmol Jacob AD et al. Kidney Int 1997; 52;

29 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin Effects of acetate on energy metabolism and function in the isolated perfused rat heart. [%] dp/dt ATP Control Acetate 10 mmol Jacob AD et al. Kidney Int 1997; 52;

30 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin Metabolic control of the circulation - Effects of acetate and pyruvate Liang et al. J.Clin.Invest. 62 November

31 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin Metabolic control of the circulation - Effects of acetate and pyruvate In summary, this study demonstrates that acetate infusion increases cardiac output, myocardial contractility, and blood flow to the myocardium, gastrointestinal tract, kidneys, and respiratory muscles. These changes, which are not seen after pyruvate infusion are probably associated with AMP formation that accompanies acetate activation. It is likely that the increase in myocardial blood flow is caused by the vasodilatory action of adenosine formed in response to the increase in AMP. Acetate may also play a role in the hemodynamic changes produced by ethanol. Our results suggest the need for an investigation of possible circulatory effects of acetate-containing dialysates in clinical use. Liang et al. J.Clin.Invest. 62 November

32 Plasma acetate, gluconate and interleukin-6 profiles during and after cardiopulmonary bypass: a comparison of Plasma-Lyte 148 with a bicarbonate-balanced solution Davies et al. Critical Care 2011, 15:R21

33 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin Acetate intolerance is mediated by enhanced synthesis of Nitric Oxide by Endothelial Cells. Nitric oxide Acet: acetate dialysis buffer (acetate 38 mmol/l) Bic: bicarbonate dialysis buffer; Bicarbonat 35 mmol/l; acetate 4 mmol/l) AFB: acetate - free dialysis buffer LPS: Lipopolysacharide) Amore et al. J Am Soc Nephrol 8; 1997

34 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin Acetate intolerance is mediated by enhanced synthesis of Nitric Oxide by Endothelial Cells. TNF-alpha Acet: acetate dialysis buffer (acetate 38 mmol/l) Bic: bicarbonate dialysis buffer; Bicarbonat 35 mmol/l; acetate 4 mmol/l) AFB: acetate - free dialysis buffer LPS: Lipopolysacharide) Amore et al. J Am Soc Nephrol 8; 1997

35 Klinik Klinik für Anästhesiologie für Anästhesiologie und Intensivmedizin Adäquat gepowerte randomisierte klinische Studien im chirurgischen Setting mit relevanten Endpunkten zu... Ringer - Azetat/Gluconat vers. Ringer - Laktat? Ringer - Azetat vers. Ringer - Laktat? Ringer - Azetat vers. Na-Bic gepuffert? Ringer - Azetat vers. Ringer - Malat?

36 Effects of Different Crystalloid Solutions on Hemodynamics, Peripheral Perfusion, and the Microcirculation in Experimental Abdominal Sepsis Peritonitis was induced by injection of autologous feces in 21 anesthetized, mechanically ventilated adult sheep. Orbegozo et al. Anesthesiology 2016; 125:744-54

41 Rolle von balanzierten Lösungen im Rahmen der Volumentherapie Physiologische Überlegungen legen nahe, bei einer Volumentherapie eine Hyperchlorämie zu vermeiden: Metabolische Azidose und hämodynamische Instabilität Chlorid - GFR - AKI Prospektive Studien scheinen die positiven Ergebnisse retrospektiver Kohortenanalysen NICHT zu bestätigen!! S3 - Leitlinie überarbeiten?? Klinische Relevanz der Anionen (Laktat, Acetat) bislang ungeklärt. Zunehmende Hinweise, dass Acetat nicht inert ist. Vielleicht doch besser einfach nur Bikarbonat!!?? CVVH -Substitutionslösung!! Je nach Sichtweise: Dringender Bedarf für größere RCTs Beweis fehlender Sinnhaftigkeit sog. evidenzbasierten Medizin